RELEVANCE OF BLOOD DATA
The overall importance and relevance of such toxicological data is emphasized eloquently by Prouty, et. al., as "One of the most fundamental questions of postmortem forensic toxicology is...'How much drug did the decedent take?' Historically, to answer this question, toxicologists have relied upon published case reports of fatal intoxication, in which the amount of ingested drug was known or reasonably approximated, and upon reports in the clinical literature that contain information concerning drug concentrations after single or chronic dosing. In recent years, pharmakokinetic equations have been increasingly used in an effort to estimate more precisely the total amount of a drug in the body and, subsequently, estimate the dose of the drug required to produce a measured blood concentration." (76). The use of blood morphine levels to establish criminal intent dates back over 100 years. Nakamura points out that "As early as 1893...Thorwald describes a celebrated court proceeding involving a physician who allegedly poisoned his wife with morphine." (63).

BLOOD IS LIKE AN HONEST WITNESS
Analyzing the morphine level of a dead person can help determine the time and the manner of death. Such tests are useful in cases where there is no eyewitness, or, for example, in the Cobain case, where there are officially no witness, but where forensic evidence suggests the presence of a witness, i.e. Cobain was either dead or so severely incapacitated by the massive dose heroin, that someone else had to have pulled the trigger. Nakamura remarks similarly that "Many...witnesses are unavailable because they either flee from the scene upon the death of their companion or they discard the body in a location less discriminating than their own domicile." (63) Thus the very idea of investigating a suspicious death using forensic testing of the morphine levels is a well established phenomenon, due at least partly to the tendency of those associated with the event to flee, discard the body elsewhere, and provide otherwise unreliable information in an attempt to avoid implication of their involvement. With respect to Nakamura's comment regarding "...they discard a body in a location less discriminating than their own domicile," it is noteworthy that Cobain's body was suspiciously enough found in his own domicile, even though he was supposedly a "missing person."

2.) INCAPACITATED OR DEAD BEFORE GUNSHOT:

HEROIN IS VERY FAST ACTING
The following quotes from Krivanek describe the rapid action of this deadly narcotic, especially when taken intravenously, "Heroin has a far more positive slope than either morphine or methadone- that is, its effects begin, and reach a peak more rapidly...3 mg of heroin...given by subcutaneous injection will provide adequate analgesia in about 70 per cent of patients with moderate to severe pain. At that dose sedative effects and respiratory depression should both be minimal. As dose increases, they become more pronounced, and the respiratory depression will become life-threatening with about 30 mg morphine (9 - 10 mg heroin, ed.) ...Intravenous doses, on the other hand, can be considerably smaller, - about one-fifth of the subcutaneous dose." (53). Additionally, Platt remarks on the amazing rapid action of intravenous heroin by explaining that "...the high uptake of heroin...indicates that an abrupt entrance of heroin into brain tissue probably occurs 10 to 20 seconds after the usual intravenous injection by addicts...15 seconds, 68% uptake into brain with heroin compared to 42% for methadone, 24% for codeine, and morphine too small to measure. " (75). It would be a mistake to think that even a severe addict could intravenously inject triple the maximum lethal dose of heroin and survive 10 to 20 seconds. First, it must be understood that the injection process itself takes a considerable amount of time such that the lethal effects of the drug often take effect with the needle still in the arm. This specific case supposedly involved the injection, the removal of the needle & tourniquet, the placement of paraphernalia in a box, sitting on the floor, and positioning and firing the shotgun. Secondly, it is important to note that an intravenous heroin overdose is very different from the previously described "usual injection" because an overdose produces much more serious effects much faster than the "usual injection".

SOME DATA ON SPEED OF DEATH
The Lange manual for Poisoning & Drug Overdose states that for opiates, "with higher doses, coma is accompanied by respiratory depression and apnea often results in sudden death." (68). Basically, a high lethal dose of heroin will either cause immediate death, or, in an unlikely scenario, immediate incapacitation by rendering the recipient comatose. This is described by Staub, et. al. as follows: "...we have shown that in 85% of the cases, the death should be attributed to a so-called 'golden shot'. In the remaining cases, the death is not so rapid and a survival period in a comatose state has to be taken into consideration." (90). Similarly, Garriot & Sturner, describe how "...morphine in the blood was found to correlate with the time of survival and ranged from 10 to 93 mcg per 100ml (.1 to .93 mg per litre, ed.) in the short-term interval group." (28). Notably, as of 1973, Garriott & Sturner did not find any blood morphine level over 0.93 mg per litre, i.e. Cobain's blood level was over 50% higher than the highest level they had ever encountered. Regarding the common sequelae of heroin overdoses, Nakamura explains " there are vivid accounts of victims lapsing into a deep coma immediately following a 'fix' with a syringe still afixed in the arm or on the floor underneath the body, and/or with an improvised tourniquet still in place around the arm." (63). Gossell & Bricker report that "for a large overdose, the victim rapidly lapses into coma and is not arousable by verbal or painful stimuli." (32).

ACUTE HEROIN OVERDOSES ARE DOSE RELATED
Garriott & Sturner describe the relation between dose and speed of death as follows: "The cases in the intermediate-survival range - namely, from three to 24 hours - showed values for morphine in the blood of 3 to 10 mcg per 100 ml (.03 to .1 mg per litre, ed.). ...It is of interest that the three cases in the short-survival group demonstrating the highest concentrations of morphine in the blood (50, 50, and 93 mcg per 100 ml) (0.5, 0.5, and 0.93 mg per litre, ed.) showed neither froth in the air passages nor extensive pulmonary edema, supporting the concept that a very sudden death may be due to other mechanisms after injection. Rapid central-nervous-systems and respiratory depression as a direct effect of the narcotic drug would account for this phenomenon. ...(ed. note: as of 1973) The highest observed blood morphine value in an acute heroin "overdose" is 100 mcg per 100 ml (1 mg per litre, ed.). ...relatively high concentrations of free morphine tend to indicate the importance of the final injection in producing the lethal reaction." (28). Nakamura explains "In more cases, it can be now shown that narcotic was taken and rapidly distributed by the body to the various organs, and it may now be unnecessary to explain narcotic deaths by blaming excipients or hypersensitivity responses." (63). Thus, although some rare overdoses can be attributed partially to hypersensitivity, allergic, and other reactions to adulterants in street heroin, it is now widely accepted that heroin overdoses are primarily dose related.

DEFINING THE PROCESSES OF DEATH
Some confusion exists in the literature regarding estimates of "speed" of death following intravenous heroin overdose, primarily due to two reasons. The first reason for confusion concerns the minimum lethal dose, i.e. a small blood morphine level does not rule out instant collapse or death. The second reason for confusion concerns the true nature of death, which technically involves the death of different organs over a period of time. Burgess describes this as "Death does not occur all at once. One organ or system of organs may die some time before another." (8). Thus, even in those rare cases when an addict takes a large overdose and does not immediately die, immediate incapacitation occurs via a coma, and a comatose person may continue to technically "live" for hours or even days. The variability in survival periods specifically concerns the lower doses, not the higher doses, and when it comes to "massive" doses, eg. the Cobain case, the data is remarkably clear in stating that such a dose would immediately incapacitate even a heroin addict with the highest of tolerance levels.

JAMES INQUEST LEADS TO CHANGED VERDICT
One specific case which bears special significance with regard to the Cobain case is the case of Cindy James. The James case, as described by Dinn (20), involves the tragic death of a nurse who was reported as missing for two weeks before she was found dead. The case was changed from a suicide verdict to a verdict of "undecided," and the basic point of comparison concerns the methodologies used to reach the change in verdict. Before continuing with the similarities between the James case & the Cobain case, it is important to note several differences. The James Case did not involve a gun, there was no drug paraphernalia found near the body, and there was evidence that she was mentally unstable and possibly staged her own death to appear as murder. Also, James received morphine, not heroin (heroin is significantly faster and stronger than morphine). The cases are similar in that both James and Cobain died of a massive drug overdose which appeared to police, initially at least, to be suicides, and which later, to varying degrees, were suggested to be homicides based significantly upon the massiveness of the overdoses in relation to degree of incapacitation and speed of death.

IMPORTANT PRECEDENT OF METHODOLOGY
It was conclusively determined that if the scenario of intravenous injection was indeed true, then "Following an injection, morphine at this concentration would have induced a rapid state of unconsciousness and death...Given the level of consciousness and the time required to create the scene...then the death would appear to have been a homicide." (20). Thus it is important to note that the only reason the case was not then determined to be a homicide is because there was no way to verify whether the morphine was taken orally or otherwise. The mere possibility of murder was enough to change the James verdict to "undecided," even though the case involved significant evidence of suicide. The James case establishes an important precedent of methodology, which is that the blood levels of morphine can be used to determine time of death and/or incapacitation with regards to recreating the events surrounding the death in question for the purposes of determining whether the death was due to murder or suicide. The same methodology, when applied to the Cobain case, indicates that due to death or incapacitation following the intravenous injection of a massive lethal dose of heroin (much stronger than morphine), Cobain's death would be even more certainly a homicide.

THE HIGHER THE DOSE, THE FASTER THE DEATH
Nakamura conducted a study in which he "..selected for toxicologic analyses seven cases of heroin fatalities in Los Angeles County, all of whom had a common history of what appeared to be sudden death. ...The blood level of morphine ranged from 0.2 to 1.0 mcg/ml." (0.2 to 1 mg per litre, ed.). "Blood morphine levels in most acute heroin-involved deaths range from 0.1 to 1.0 mcg/ml (0.1 to 1.0 mg per litre, ed.)...Blood levels of morphine also appear to be regulated by dosage." (63). Only one case in the 7 case study by Nakamura had a blood morphine level in Cobain's range, at 1.8 mg per litre, and the next closest was 0.9 mg per litre. The rest were 0.5 mg per litre and lower, with levels as low as 0.1 mg per litre causing immediate death. Nakamara also refers to his related 1974 doctoral thesis from the School of Criminology at the University of California, Berkely, where he "...examined blood specimens from 64 fatalities...whose survival time could be estimated." The highest blood morphine level was 0.8 mg per litre, and there was a clear indication that the higher the dose, the faster the death.

3.) OTHER FACTORS ENSURED OVERDOSE LETHALITY:

COMPENSATING FOR BODY WEIGHT A blood morphine level of 1.52 mg/L indicates a heroin intake of approximately 225 mg - 240 mg. Thus, despite suggestions that Cobain may have simply been incapacitated by a normal, large dose fit for an addict, it must be noted that his body weight was at highest 130 lbs., and he was listed as being 115 lbs. in late 1993. This would generally increase his susceptibility to overdose by as much as 20%, since toxicity data is based on a 150 lb. adult.

COMPENSATING FOR ADULTERATION Heroin purity has been shown to vary widely, with samples containing as little as 1% heroin. Mexican black tar is usually no higher than 40% pure, but is not uncommonly up to 80% pure, while highest recorded purity level for Mexican black tar heroin is 93% pure (89). If the heroin used in this case was indeed Mexican black tar heroin, and it was in the range of the highest potency recorded, i.e. 93% purity, then the dose required to reach a blood morphine level of 1.52 mg per litre would be approximately 245 mg to 260 mg. Whatever the physical source of heroin was, it does not really matter; the only thing that makes one type of heroin stronger than another is concentration of dose, so it was approximately 225 mg to 240 mg of some type of heroin. If the purity was 40%, a more common figure, then the lethal dose, including adulterants, would have been around 600 mg. Thus there is a definite chance of up to 350 mg of procaine or acetyl procaine as an adulterant. Note that procaine is commonly found in samples of Mexican black tar heroin. Regarding the potential toxicity of procaine, it should be noted that procaine levels would likely be undetectable in Cobain's blood due to the fact that the body was found at least three days after death. Still, the importance of procaine's potential toxicity is emphasized by Nakamura, who says "Nearly all the contraband heroin in the western areas is obtained from Mexico and contains an appreciable amount of procaine, or acetyl-procaine, as a filler material. ...The potential danger of a large concentration of this dilutent in street heroin needs to be better understood. (63).

THE SIGNIFICANCE OF DIAZEPAM PRESENCE Diazepam is generally synonymous with the more well-known drug Valium, and sometimes the term diazepam refers to the generic category of drugs known as benzodiazepines. This class of drugs is regarded as sedative-hypnotic, and is not cross-tolerant to opioids. That means addicts can use diazepam and similar drugs in the same way that non-addicts use them. Conversely, even a heroin addict will experience toxicity to benzodiazepines in the same manner as a non-addict. A junkie is not immune to the toxic effects of a benzodiazepine overdose simply because he or she can handle a big dose of heroin. Cassidy, et. al. report "as both drugs cause respiratory depression...the likelihood of death resulting as a consequence...is greater than if either drug were taken alone." (10). Oldendorf reports on the effect of relaxation as increasing heroin absorption in the brain (67), a factor which addicts often attempt to manipulate, eg. by using heroin with a relaxant such as a benzodiazepine.

BENZODIAZEPINES & HEROIN COMMON PARTNERS IN DEATHS Diazepam poisoning in particular, and benzodiazepine poisoning in general, is rare in isolation, but not at all uncommon in combination with other similar drugs, notably heroin. Several current studies from sources as disparate as the USA, Australia, Denmark, and the U.K., show that benzodiazepine abuse frequently occurs with heroin abuse, and that resultant death is a serious, growing concern. The two drugs have a definite added effect, increasing the likelihood of respiratory failure associated with heroin overdose by a very significant amount, which has now been relatively well quantified. The lethality of the combined use of heroin and diazepam are discussed by Nakamura, who mentions them in reference to occasional problems with finding a postmortem blood morphine level. The lethality of the heroin is so greatly increased that very small doses kill, meaning that "...the interaction of drugs in eliciting acute responses and causing deaths even when sublethal amounts of two or more drugs are present in postmortem specimens from the same cadaver may be a factor." (63).

THE POSSIBILITY OF FAST-ACTING BENZODIAZEPINES
The previous relative safety of benzodiazepines has become especially challenged lately with the misuse and abuse of related drugs such as Halcion and Xanax. Notably, these newer ultra-short acting benzodiazepines have a much shorter half-lives. This means that they clear out of the body very fast. Also, they have been considered the sole cause of death in recent forensic cases. Their potential lethality is especially increased when injected, and is the most common form of benzodiazepine-related respiratory failure. While diazepam is effective at a dose of 5 mg, the effective dose of Xanax is merely 250 mcg, with a half-life of 10-20 hours. Thus Xanax works as well as Diazepam at one-twentieth of the dose. Diazepam works in 30 minutes, while Xanax works immediately, and has a half-life of 10-20 hours. That means that 10-20 hours after taking it, half of it has been rendered useless. When injected, benzodiazepines in general are twice as potent. Thus a significantly toxic oral dose of 30 mg of diazepam would be easily achieved by an approximate equivalent of 500 mcg to 750 mcg of intravenously administered Xanax. Diazepam is measured usually by its secondary metabolites in the liver, and the metabolites for Xanax and Diazepam and Valium are all very similar, so often no differentiation is made during testing, which is often only conducted to determine presence, not quantity. If the benzodiazepine in Cobain's blood was indeed a fast-acting one, then it very likely played a major role in making the massive dose of heroin even more deadly.

SOME DEATHS INVOLVING HEROIN & DIAZEPAM
Gottschalk and Cravey, in their large compilation of deaths involving psychotropic drugs, found 129 cases where morphine, predominantly intravenous heroin, was determined to be the primary cause of death. Three of these cases involved diazepam and intravenous heroin or morphine (33). The first and second cases both involved oral diazepam plus intravenous heroin and/or morphine. The first case showed a blood morphine level of only 0.13 mg/L and diazepam at 1.4 mg/L, and the body was discovered approximately nine hours after death. Case 2 showed 0.3 mg/L blood morphine and 6 mg/L diazepam, and was discovered about seven hours after death. Case 3 included the possibility that the diazepam might have been injected with the morphine, and the blood levels were 0.02 mg/L morphine and 0.3 mg/L diazepam, with the body discovered about 24 hours after death. The third case in particular shows an extremely low blood morphine level can be lethal when combined with a low dose of diazepam.

4.) CASE UNPARALLELED IN SUICIDE & OVERDOSE REPORTS:

VERY HIGH BLOOD MORPHINE LEVELS ARE RARE
As mentioned previously, the strongest forensic evidence indicating Cobain was murdered is the sheer lack of a parallel case in forensic literature concerning violent suicides and/or overdoses. Overdose reports normally show results similar to those from Logan & Luthi, who described 16 deaths caused by intravenous heroin or morphine in which blood levels were measured, and the highest serum morphine level seen was 0.920 mg/L. (57). Appendix A: Compendium of Intravenous Heroin Related Deaths Where Blood Morphine Levels Were Measured, shows the rarity of occurrence of a blood morphine level equal to or greater than Cobain's. Many thousands of opiate related deaths were reviewed, and for the purposes of this report, over 3000 of these deaths were determined to be specifically related to overdoses among addicts involving the intravenous use of morphine or heroin. Next, this group was further narrowed to eliminate those cases in which blood morphine levels were not available. Cases where the drug was known to be morphine were eliminated, as were cases where the cause of death was determined to be other than overdose. The 1526 cases remaining showed 26 instances where the blood morphine levels were equal to or above Cobain's, an occurrence rate of 1.7%. None of the above cases reportedly involve a gun or violent suicide. Additionally, no case reported overdose sequlelae of a nature which would even imply the possibility of anything other than immediate incapacitation and/or death. Where data was available, it was remarkably clear in presenting images of addicts with tourniquets in place, syringes in hand, and other evidence of abrupt death. Clearly, the level found in Cobain is among the top 2% of the highest blood morphine levels ever discovered, even in severe addicts.

SELF-POISONING & VIOLENT SUICIDE RARE AMONG ADDICTS
The fact that the Cobain case as it supposedly happened has no parallel in the references reviewed concurs with Burston's finding that "self-poisoning with morphine or heroin is very uncommon." (9). He also states the effects of heroin "...is of such short duration and is so intense that it inhibits any type of physical activity, either criminal or non-criminal." (9). Also, no case of violent or traumatic suicide reviewed compared well with the Cobain case. Gatter studied "...1862 postmortem examinations of suicides carried out in north west London over a 20 year period from 1957-1977...," (29) with only 20% (369 cases) committing suicide by physical injury, none of which involved opiates. Maurer and Vogel state plainly "...the general rule that opiates inhibit tendencies toward violence." (59). Similar findings are reported by Nowers, in his study of "...51 consecutive gunshot suicides in the County of Avon, England between 1974 and 1990," where it is apparent that suicide by gunshot is uncommon. "Of the 1,117 cases identified, 51 were gunshot suicides (4.5 per cent)...39 used a shotgun." (65). Again, no case reported blood morphine levels. This is illustrated in Table 5, below.